This is a proposal to develop novel short-acting selective agonists of A2A adenosine receptors as pharmacologic stress agents to detect coronary artery disease. Such agents are increasingly being employed as an alternative to exercise stress in patients undergoing nuclear or echocardiographic imaging. in 1999, it is estimated that 1.7 million people in the United States alone will undergo pharmacologic stress. Currently used agents, adenosine or dipyridamole, cause a significant number of adverse side effects including chest pain, A-V conduction block, hypotension, and bronchospasm. The desired coronary vasodilatation is mediated by the stimulation of the adenosine A2A receptor by adenosine, most of the side effects are caused by stimulation of the other 3 adenosine receptor subtypes: Al, A2B, and A3. The goal of this proposal is to evaluate a new class of very potent, highly selective, short-acting agonists of the adenosine A2A receptor as vasodilators for pharmacologic stress perfusion imaging. The potency, selectivity and short duration of these compounds should reduce or eliminate the severe side effects currently associated with vasodilator stress, and increase patient comfort and safety. PROPOSED COMMERCIAL APPLICATION: This technology will be commercialized by a new Biotechnology start-up company, Adenosine Therapeutics, LLC.